The AT2 Receptor Selectively Associates with Giα2 and Giα3 in the Rat Fetus

The effects of angiotensin II are mediated by a family of seven transmembrane receptors. In the adult, the majority of the receptors are of the AT1 isoform, which is coupled to heterotrimeric G proteins (either Gqα or Giα). In contrast, the AT2 receptor is expressed at low levels in the adult but is the major form expressed in the fetal and neonatal animal. Previous results have failed to show G protein coupling of the AT2 receptor in the fetus. We now provide evidence that the AT2 receptor is G protein-coupled. An antibody that binds several Gα subunits immunoselected angiotensin II receptor-Gα complexes. In addition, Giα1-3 antibody, which recognizes Giα1, Giα2 and Giα3, also co-immunoselect the AT2 receptor. Anti-Giα2 and anti-Giα3 antibodies were both able to co-immunoselected AT2 receptor-Giα complexes, but consistent with the lack of Giα1 in the fetal extracts, anti-Giα1 antibodies did not nor did any other G protein-directed antisera. The finding that AT2 receptor couples to both Giα2 and Giα3 raises the possibility that selective interactions between AT2 receptor and different G proteins may result in specific cellular effects mediated by AT2 stimulation.